title: Tobacco smoke-induced skin pigmentation is mediated by the aryl hydrocarbon receptor.
abstract: It is widely recognized that tobacco smoke causes skin pigmentation. No studies, however, have directly evaluated the mechanisms of the changes in smoker's skin pigmentation. In this study, when cultured with water-soluble tobacco smoke extract, the human epidermal melanocytes grew to a large size and produced more melanins. We evaluated melanocyte activation by quantifying microphthalmia-associated transcription factor (MITF) expression by real-time polymerase chain reaction. MITF expression was significantly and dose-dependently increased by exposure to tobacco smoke extract. The Wnt/β-catenin signalling pathway seemed to mediate the tobacco smoke extract-induced melanocyte activation. Immunocytochemical studies revealed that the activated melanocytes actively expressed aryl hydrocarbon receptors (AhR) around the nuclear membrane. The tobacco smoke extract-induced MITF activation was inhibited by RNA silencing of the AhR. This study provides the evidence that tobacco smoke enhances pigmentation in vitro and that the increase in pigmentation may involve β-catenin- and AhR-mediated mechanisms inside human melanocytes.
authors.forename: Motoki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ueda
authors.forename: Mai
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
authors.forename: Takuya
authors.initials: T
authors.lastname: Furuhashi
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012880:Skin Pigmentation / Q000187:drug effects*; D012906:Smoke; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D014026:Nicotiana
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051739:Microphthalmia-Associated Transcription Factor; D012313:RNA; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke; D051176:beta Catenin; C111235:AHR protein, human; C495270:CTNNB1 protein, human; C497234:MITF protein, human
keywords: aryl hydrocarbon receptor; melanocyte; pigmentation; tobacco smoking; β-catenin